Collisions during DNA replication and transcription contribute to mutagenesis

June 29, 2016

Credit: NIH

When a cell makes copies of DNA and translates its genetic code into proteins at the same time, the molecular machinery that carries on replication and the one that transcribes the DNA to the mRNA code move along the same DNA double strand as their respective processes take place. Sometimes replication and transcription proceed on the same direction, but sometimes the processes are in a collision course. Researchers at Baylor College of Medicine and the University of Wisconsin have determined that these collisions can significantly contribute to mutagenesis. Their results appear today in Nature.

"We first developed a laboratory assay that would allow us to detect a wide range of mutations in a specific gene in the bacteria Bacillus subtilis," said corresponding author Dr. Jue D. Wang, who was an associate professor of molecular & human genetics at Baylor when a portion of the work was completed and is currently with the University of Wisconsin, Madison. "In some bacteria, we introduced the gene so the processes of replication and transcription would proceed on the same direction. In other bacteria the gene was engineered so the processes would collide head-on."

The researchers discovered that when replication and transcription were oriented toward a head-on collision path the mutation rate was higher than when their paths followed the same direction. Furthermore, most of the mutations caused by replication transcription conflicts were either insertions/deletions or substitutions in the promoter region of the gene, the region that controls gene expression.

"People have mostly been looking at mutations in the DNA sequence that codes for protein, but in this paper we found that the promoter, the regulatory element of gene expression, is very susceptible to mutagenesis," said Wang, "and this susceptibility is facilitated by head-on transcription and DNA replication."

Promoters control how much of a gene is transcribed; for instance, particular mutations in promoters may enhance or reduce the production of proteins, or silence them completely. These genetic changes in gene expression may affect an organism's health.

"The mutation mechanism we identified is not just applicable to our experimental system, but can potentially contribute to mutations that alter gene expression in a genome-wide scale, from bacteria to humans," said Wang.

Related Stories

Bacteria appear to speed up their evolution by positioning specific genes along the route of expected traffic jams in DNA encoding. Certain genes are in prime collision paths for the moving molecular machineries that read ...

In a study published on 28 March 2016 in the Proceedings of the National Academy of Sciences, researchers at the Medical University of South Carolina (MUSC) and Virginia Commonwealth University have resolved the first protein ...

A research collaboration between the Medical University of South Carolina, the Institute of Human Genetics in France, and Howard Hughes Medical Institute at Rockefeller University has revealed the means by which cells accomplish ...

(Phys.org)—The majority of the human genome is located within the nucleus. However, there is a small but important portion of DNA located within the mitochondria. This mitochondrial DNA (mtDNA) has received much attention ...

DNA replication, the process by which a strand of DNA is copied during cell proliferation , and DNA transcription, the process by which the message in the DNA is translated into messenger RNA, involve the same "track" or ...

Cancer development is a complex process involving both genetic and epigenetic changes. Genetic changes in oncogenes and tumor-suppressor genes are generally considered as primary causes, since these genes may directly regulate ...

The comfort food we know and love today as the potato was domesticated between 8,000 and 10,000 years ago from a wild species native to the Andes Mountains in southern Peru. During the 16th century, Spanish conquistadors ...

Wild-derived house mice call at higher rates and frequencies during interactions with the opposite sex than with the same sex, according to a study published December 13, 2017 in the open-access journal PLOS ONE by Sarah ...

Researchers from Cardiff University's Otter Project have discovered that genetically distinct populations of wild otters from across the UK have their own regional odours for communicating vital information to each other. ...

0 comments

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.